tbuckley/cabot-search huggingface dataset:
Genetic Polymorphism of 5,10-Methylenetetrahydrofolate Reductase (MTHFR) as a Risk Factor for Coronary Artery Disease
Authors: Hiroyuki Morita, Jun-ichi Taguchi, Hiroki Kurihara, Masao Kitaoka, Hideaki Kaneda, Yukiko Kurihara, Koji Maemura, Tohru Minamino, Minoru Ohno, Kazuhide Yamaoki, Ken Ogasawara, Tadanori Aizawa, Shin Suzuki, Yoshio Yazaki
Journal: Circulation (1997)

Background Epidemiological studies have identified hyperhomocyst(e)inemia as an independent risk factor for coronary artery disease (CAD). Recently, the alanine/valine ( A/V ) polymorphism of the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene, one of the key enzymes catalyzing remethylation of homocysteine, has been reported. The VV genotype correlates with increased plasma homocyst(e)ine levels as a result of the reduced activity and increased thermolability of this enzyme. In this study, we examined the distribution of the MTHFR genotypes in Japanese men and the association between the VV genotype and CAD. Methods and Results The diagnoses of CAD of all the studied patients were confirmed by coronary angiography. The MTHFR genotype was analyzed by PCR followed by Hin fI digestion. In 778 healthy male subjects, the frequency of the V allele was 0.33, comparable to that in a French Canadian population. In 362 patients with CAD, the VV genotype was significantly more frequent than in control subjects (16% versus 10%, P =.0067). The association of the VV genotype with CAD was further increased in patients with ≥99% stenotic lesions (18%, P =.0010), whereas no significant association with the VV genotype was observed in patients without a ≥99% stenosis. When the genotype frequency was compared among patients with different numbers of stenotic coronary arteries, the frequency of the VV genotype was significantly higher in patients with triple-vessel disease (26%) than in patients with single- or double-vessel disease (15% and 14%, respectively). Conclusions The VV genotype of MTHFR was also common in the Japanese population and was significantly associated with CAD. The frequency of this genotype in particular was correlated with the severity of disease. The VV genotype associated with a predisposition to increased plasma homocyst(e)ine levels may represent a genetic risk factor for CAD.
Association of Prior Infection With Chlamydia pneumoniae and Angiographically Demonstrated Coronary Artery Disease
Authors: David H. Thom
Journal: JAMA (1992)

<h3>Objective.</h3> —To evaluate the association between prior infection with<i>Chlamydia pneumoniae</i>, as measured by IgG antibody, and coronary artery disease. <h3>Design.</h3> —A population-based, case-control study. <h3>Setting.</h3> —Group Health Cooperative of Puget Sound, a Seattle-based health maintenance organization. <h3>Participants.</h3> —Men 55 years of age and younger and women 65 years of age and younger. Cases (n=171) were members of Group Health Cooperative undergoing diagnostic coronary angiography who had at least one coronary artery lesion occupying 50% or more of the luminal diameter. The population controls (n=120) were Group Health Cooperative members without known coronary heart disease. <h3>Main Outcome Measure.</h3> —The adjusted odds ratio (OR) for coronary artery disease associated with prior<i>Cpneumoniae</i>infection as measured by the presence of IgG antibody. <h3>Results.</h3> —After adjusting for age, gender, and calendar quarter of blood drawing, the OR for coronary artery disease associated with the presence of antibody was 2.6 (95% confidence interval, 1.4 to 4.8). The association was limited to cigarette smokers, in whom the OR was 3.5 (95% confidence interval, 1.7 to 7.0). Among never-smokers, the OR was 0.8 (95% confidence interval, 0.3 to 1.9). When cases and controls were restricted to those assayed concurrently, the adjusted OR (smokers and nonsmokers combined) was 4.2 (95% confidence interval, 1.8 to 10.0). Adjustment for serum cholesterol, hypertension, alcohol use, diabetes, and socioeconomic status did not change these results. Only a weak association was found when cases were compared with 63 subjects whose angiographic results were normal (OR, 1.2; 95% confidence interval, 0.6 to 2.2). <h3>Conclusions.</h3> —These results generally support the previously reported association between<i>Cpneumoniae</i>infection and coronary heart disease. However, caution should be used in interpreting the basis for this association. (<i>JAMA</i>. 1992;268:68-72)
An open-label, dose-ranging study of methotrexate for moderate-to-severe adult atopic eczema
Authors: S.C. Weatherhead, S. Wahie, N.J. Reynolds, S.J. Meggitt
Journal: British Journal of Dermatology (2007)

Background Treatment options for moderate-to-severe atopic eczema are limited. Although methotrexate (MTX) is a widely used and effective treatment for psoriasis, there have been no previous prospective trials of its use in refractory atopic eczema, despite a few small, retrospective reports suggesting that it is a well-tolerated and effective treatment. Objectives We have assessed the safety and efficacy of oral MTX in 12 adults with moderate-to-severe atopic eczema in an open-label, dose-ranging, prospective trial using objective outcome measures. Methods All patients had previously received other second-line therapies and had disease only partially responsive to potent topical steroids and emollients. During the 24-week MTX treatment period, unrestricted use of standard topical therapy was permitted. We used an incremental MTX dose regime, starting at 10 mg per week (following a 5-mg test dose) and increasing by 2·5 mg weekly until response was achieved or treatment was limited by toxicity. Disease activity [six area six sign atopic dermatitis (SASSAD) score] was assessed every 4 weeks during treatment and 12 weeks after stopping MTX. The primary endpoint was 24-week change in disease activity. Results On average, disease activity improved by 52% from baseline (95% confidence interval 45–60%). There were significant improvements in quality of life, body surface area affected and loss of sleep and itch scores. Global response was rated as 'marked improvement' in five of 12 and six of 12 patients, by investigators and patients, respectively. In all patients, the majority of improvement in disease activity was seen by week 12, and, interestingly, patients who had not responded well over this period despite reaching a dose of 15 mg weekly failed to improve with further dose escalation. Only one patient withdrew due to minor adverse effects. MTX was well tolerated by the remaining 11 patients, all of whom completed treatment, achieving a median dose of 15 mg weekly. Importantly, eight of nine patients had a persistent improvement 12 weeks after stopping MTX, with mean disease activity remaining 34% below baseline. Conclusions We have shown that MTX is an effective, well-tolerated treatment for moderate-to-severe atopic eczema, and response appears to compare favourably with other second-line therapies. A randomized, controlled trial is now warranted.
Bronchoalveolar Lavage and Transbronchial Biopsy for the Diagnosis of Pulmonary Infections in the Acquired Immunodeficiency Syndrome
Authors: COURTNEY BROADDUS
Journal: Annals of Internal Medicine (1985)

The efficacy of bronchoalveolar lavage and transbronchial biopsy in diagnosing lung infection was determined in 276 fiberoptic bronchoscopic examinations done on 171 patients with known or suspected acquired immunodeficiency syndrome. Of 173 pathogens (Pneumocystis carinii, cytomegalovirus, Mycobacterium avium-intracellulare, Cryptococcus neoformans, M. tuberculosis, Coccidioides immitis, and Histoplasma capsulatum) identified during the initial evaluation or in the subsequent month, the initial bronchoscopic examination detected 166 (96%). Bronchoalveolar lavage and transbronchial biopsy had sensitivities of 86% and 87%, respectively. When bronchoscopy included both bronchoalveolar lavage and transbronchial biopsy, the yield for all pathogens was 98% and the sensitivity for P. carinii infections was 100%. Follow-up for at least 3 weeks after examination failed to detect any additional false-negative results. Fiberoptic bronchoscopy is extremely accurate for the detection of pathogens in patients with the acquired immunodeficiency syndrome, especially when bronchoalveolar lavage and transbronchial biopsy are combined. In patients at high risk of complications from transbronchial biopsy, bronchoalveolar lavage is sufficiently accurate to be used alone.
Single versus Double Autologous Stem-Cell Transplantation for Multiple Myeloma
Authors: Michel Attal, Jean-Luc Harousseau, Thierry Facon, François Guilhot, Chantal Doyen, Jean-Gabriel Fuzibet, Mathieu Monconduit, Cyrille Hulin, Denis Caillot, Reda Bouabdallah, Laurent Voillat, Jean-Jacques Sotto, Bernard Grosbois, Regis Bataille
Journal: New England Journal of Medicine (2003)

We conducted a randomized trial of the treatment of multiple myeloma with high-dose chemotherapy followed by either one or two successive autologous stem-cell transplantations.
Update: Influenza Activity—United States, 1997-98 Season
Journal: JAMA (1998)

From the Centers for Disease Control and PreventionLeads From the Morbidity and Mortality Weekly Report Atlanta, Ga pected measles cases were reported from the countries.Of these, 27,635 (31%) have been confirmed, 33,120 (37%) have been discarded, and 27,730 (31%) are under investigation.Of the 27,635 confirmed cases in 1997, a total of 26,919 (97%) were confirmed by laboratory testing or linked epidemiologically to a laboratory-confirmed case, and 716 (3%) were confirmed clinically, without laboratory investigation.Brazil (26,348 confirmed cases) and Canada (570 confirmed cases) accounted for 97% of the total confirmed cases in the region.The United States (135 cases), Paraguay (198), Guadeloupe (116), Argentina (96), Chile (59), Venezuela ( 27), and Costa Rica (15) all reported Ͼ10 confirmed measles cases during 1997. BrazilOf the 26,348 confirmed cases reported from Brazil, 20,186 (77%) were reported from Sa ˜o Paulo, the only state that did not conduct a follow-up measles vaccination campaign in 1995.Most cases during this outbreak occurred in persons residing in the greater Sa ˜o Paulo metropolitan area.Of the 19,322 confirmed measles cases reported from Sa ˜o Paulo for which patient age was known, 9938 (51%) occurred in persons aged 20-29 years.The highest age-specific incidence rates were reported for infants aged Ͻ1 year (456 cases per 100,000 population), young adults aged 20-29 years (156), and children aged 1-4 years (45).Many cases occurred among young adults who were members of groups congregating in enclosed environments, including male migrant workers from rural areas, students, health-care workers, tourist industry workers, and military recruits.Twenty measles-related deaths were reported; 17 (85%) occurred among infants aged Ͻ1 year.Genomic sequencing of virus isolates from Brazil, performed by CDC's Respiratory and Enteric Viruses Branch, demonstrated that the virus circulating in Sa ˜o Paulo was similar to virus isolates recently obtained from Western Europe, suggesting that the virus responsible for the outbreak may have been im-
Integrated Therapy for Locally Advanced Bladder Cancer: Final Report of a Randomized Trial of Cystectomy Plus Adjuvant M-VAC Versus Cystectomy With Both Preoperative and Postoperative M-VAC
Authors: Randall Millikan, Colin Dinney, David Swanson, Paul Sweeney, Jae Y. Ro, Terry L. Smith, Dallas Williams, Christopher Logothetis
Journal: Journal of Clinical Oncology (2001)

PURPOSE: We conducted a phase III trial to investigate the timing of chemotherapy with respect to surgery for patients with resectable but high-risk urothelial cancer. The trial was also designed to evaluate the accuracy of clinical staging in patients with locally advanced cancer and the prognostic significance of chemotherapy-induced downstaging. PATIENTS AND METHODS: A total of 140 uniformly evaluated patients with locally advanced urothelial cancer were studied. Planned treatment was five cycles of chemotherapy (M-VAC: methotrexate, vinblastine, doxorubicin, and cisplatin) plus radical cystectomy and pelvic lymph node dissection. Patients were randomly assigned to receive either two courses of neoadjuvant M-VAC followed by surgery plus three additional cycles of chemotherapy, or, alternatively, to have initial cystectomy followed by five cycles of adjuvant chemotherapy. RESULTS: There were no significant differences in outcome between the two groups. By intent-to-treat, 81 patients (58%) remain disease-free, with median follow-up of 6.8 years. We confirmed a high rate of clinical understaging in this cohort, especially among patients showing lymphovascular invasion on biopsy. Patients with no residual muscle-invasive disease at cystectomy after neoadjuvant chemotherapy were likely to be cured. CONCLUSION: These results lend further support to the impression from small randomized trials that, in a high-risk cohort, there is an improved cure fraction by the combination of multiagent chemotherapy and surgery, although we found no preferred sequence. Importantly, it is possible to select appropriate patients for such therapy on the basis of clinical staging information. These results establish a benchmark of outcome for this cohort.
Alpha<sub>1</sub>-Antitrypsin Deficiency
Authors: James O. Morse
Journal: New England Journal of Medicine (1978)

FIFTEEN years ago Laurell and Eriksson discovered a genetically determined deficiency in a major serum protease inhibitor.1 They also noted a striking association between the deficiency and the early onset of severe emphysema. Five years later Sharp observed a less obvious relation with childhood cirrhosis.2 Although there has been a resultant interest in seeking out persons afflicted with the deficiency to advise them on preventive measures and genetic risks, the major importance of these discoveries may lie in the clues that they have provided for basic research into the pathogenesis of emphysema and idiopathic hepatic cirrhosis. . . .
Haemophilus influenzae
Journal: BMJ (1974)

Compensation for InjuryThe Royal Comnission on Civil Liability and Compensation for Personal Injury, who began by inviting evidence on injuries suffered in the course of employment and road transport injuries, are now extending their invitation to the remaining areas of their remit.These are: death or personal injury "through the manufacture, supply or use of goods or services; on premises belonging to or occupied by anotrher; or otherwise through the act or omission of another where compensation under the present law is recoverable only on proof of fault or under the rules of strict liability.
Tumor Cell-Specific <b> <i>BRCA1</i> </b> and <b> <i>RASSF1A</i> </b> Hypermethylation in Serum, Plasma, and Peritoneal Fluid from Ovarian Cancer Patients
Authors: Inmaculada Ibanez de Caceres, Cristina Battagli, Manel Esteller, James G. Herman, Essel Dulaimi, Mitchell I. Edelson, Cynthia Bergman, Hormoz Ehya, Burton L. Eisenberg, Paul Cairns
Journal: Cancer Research (2004)

Abstract Because existing surgical and management methods can consistently cure only early-stage ovarian cancer, novel strategies for early detection are required. Silencing of tumor suppressor genes such as p16INK4a, VHL, and hMLH1 have established promoter hypermethylation as a common mechanism for tumor suppressor inactivation in human cancer and as a promising target for molecular detection in bodily fluids. Using sensitive methylation-specific PCR, we screened matched tumor, preoperative serum or plasma, and peritoneal fluid (washes or ascites) DNA obtained from 50 patients with ovarian or primary peritoneal tumors for hypermethylation status of the normally unmethylated BRCA1 and RAS association domain family protein 1A tumor suppressor genes. Hypermethylation of one or both genes was found in 34 tumor DNA (68%). Additional examination of one or more of the adenomatous polyposis coli, p14ARF, p16INK4a, or death associated protein-kinase tumor suppressor genes revealed hypermethylation in each of the remaining 16 tumor DNA, which extended diagnostic coverage to 100%. Hypermethylation was observed in all histologic cell types, grades, and stages of ovarian tumor examined. An identical pattern of gene hypermethylation was found in the matched serum DNA from 41 of 50 patients (82% sensitivity), including 13 of 17 cases of stage I disease. Hypermethylation was detected in 28 of 30 peritoneal fluid DNA from stage IC-IV patients, including 3 cases with negative or atypical cytology. In contrast, no hypermethylation was observed in nonneoplastic tissue, peritoneal fluid, or serum from 40 control women (100% specificity). We conclude that promoter hypermethylation is a common and relatively early event in ovarian tumorigenesis that can be detected in the serum DNA from patients with ovary-confined (stage IA or B) tumors and in cytologically negative peritoneal fluid. Analysis of tumor-specific hypermethylation in serum DNA may enhance early detection of ovarian cancer.
Differential Patterns of MicroRNA Expression in Neuroblastoma Are Correlated with Prognosis, Differentiation, and Apoptosis
Authors: Yongxin Chen, Raymond L. Stallings
Journal: Cancer Research (2007)

Abstract Neuroblastoma accounts for 15% of pediatric cancer deaths, and although a few protein-coding genes, such as MYCN, are involved with aggressive pathogenicity, the identification of novel biological targets for therapeutic intervention is still a necessary prerequisite for improving patient survival. Expression profiling of 157 microRNA (miRNA) loci in 35 primary neuroblastoma tumors indicates that 32 loci are differentially expressed in favorable and unfavorable tumor subtypes, indicating a potential role of miRNAs in neuroblastoma pathogenesis. Many of these loci are significantly underexpressed in tumors with MYCN amplification, which have particularly poor prognoses. Interestingly, we found that miRNA expression levels substantially change in a MYCN-amplified cell line following exposure to retinoic acid, a compound which is well known for causing reductions in MYCN expression and for inducing neuroblastoma cell lines to undergo neuronal differentiation. We also show that small interfering RNA inhibition of MYCN by itself causes similar alterations in the expression of miRNA loci. In vitro functional studies of one locus, miR-184, indicate that it plays a significant role in apoptosis. The association of experimentally induced alterations of miRNA expression in neuroblastoma cell lines with differentiation or apoptosis leads us to conclude that these loci play important roles in neuroblastoma pathogenesis. We further suggest that MYCN may mediate a tumorigenic effect, in part, through directly or indirectly regulating the expression of miRNAs that are involved with neural cell differentiation and/or apoptosis, warranting substantial further studies of miRNAs as potential therapeutic targets. [Cancer Res 2007;67(3):976–83]
Cell-based therapies for glioblastoma: Promising tools against tumor heterogeneity
Authors: Dean Nehama, Alex S Woodell, Spencer M Maingi, Shawn D Hingtgen, Gianpietro Dotti
Journal: Neuro-Oncology (2023)

Abstract Glioblastoma (GBM) is a highly aggressive tumor with a devastating impact on quality-of-life and abysmal survivorship. Patients have very limited effective treatment options. The successes of targeted small molecule drugs and immune checkpoint inhibitors seen in various solid tumors have not translated to GBM, despite significant advances in our understanding of its molecular, immune, and microenvironment landscapes. These discoveries, however, have unveiled GBM’s incredible heterogeneity and its role in treatment failure and survival. Novel cellular therapy technologies are finding successes in oncology and harbor characteristics that make them uniquely suited to overcome challenges posed by GBM, such as increased resistance to tumor heterogeneity, modularity, localized delivery, and safety. Considering these advantages, we compiled this review article on cellular therapies for GBM, focusing on cellular immunotherapies and stem cell-based therapies, to evaluate their utility. We categorize them based on their specificity, review their preclinical and clinical data, and extract valuable insights to help guide future cellular therapy development.
Performance analysis of EEG based emotion recognition using deep learning models
Authors: M Jehosheba Margaret, N.M Masoodhu Banu
Journal: Brain-Computer Interfaces (2023)

Emotion is an important factor that decides the the state of the mind of an individual. However, there are many people who cannot express their emotions explicitly due to various psychological or physiological issues. The recent technology development in interdisciplinary techniques has made the emotion recognition easy. The main objective of this paper is to uncover the contribution of hybrid deep learning model in classifying the emotions. This novel hybrid Bi-LSTM model is applied to three dimensional VAD model to classify 16 emotions. In addition, this paper addresses their performance comparison with respect to other models. Deep learning models like CNN, LSTM, Hybrid Bi-LSTM, and Hybrid Bi-GRU were used for experimentation. FFT is used to convert from time domain to frequency domain in all the models. The performance measure of these models is estimated in terms of accuracy, precision, recall, and F1score. The estimated accuracy of different deep learning models are approximated to be 87.5% for CNN, 88.7 % for LSTM, 93.9% for Hybrid Bi-LSTM, and 92.2% for Hybrid GRU based on the number of subjects. These comparisons have helped to find the suitable deep learning model for emotion recognition.
Advances of antitumor drug discovery in traditional Chinese medicine and natural active products by using multi‐active components combination
Authors: Wei Zhao, Xiao‐Di Zheng, Paula Yun‐Zhi Tang, Hong‐Mei Li, Xue Liu, Jian‐Jiang Zhong, Ya‐Jie Tang
Journal: Medicinal Research Reviews (2023)

Abstract The antitumor efficacy of Chinese herbal medicines has been widely recognized. Leading compounds such as sterols, glycosides, flavonoids, alkaloids, terpenoids, phenylpropanoids, and polyketides constitute their complex active components. The antitumor monomers derived from Chinese medicine possess an attractive anticancer activity. However, their use was limited by low bioavailability, significant toxicity, and side effects, hindering their clinical applications. Recently, new chemical entities have been designed and synthesized by combining natural drugs with other small drug molecules or active moieties to improve the antitumor activity and selectivity, and reduce side effects. Such a novel conjugated drug that can interact with several vital biological targets in cells may have a more significant or synergistic anticancer activity than a single‐molecule drug. In addition, antitumor conjugates could be obtained by combining pharmacophores containing two or more known drugs or leading compounds. Based on these studies, the new drug research and development could be greatly shortened. This study reviews the research progress of conjugates with antitumor activity based on Chinese herbal medicine. It is expected to serve as a valuable reference to antitumor drug research and clinical application of traditional Chinese medicine.